组织驻留巨噬细胞与卵巢常见疾病

doi:10.12280/gjszjk.20230024

摘要/Abstract

摘要：

卵巢内存在复杂的神经-内分泌和免疫调控网络。组织驻留巨噬细胞（tissue-resident macrophages，TRM）是一类存在于人体绝大多数组织器官、独立于外周循环且具有一定自我更新能力的固有免疫细胞，卵巢TRM是卵巢中最丰富的免疫细胞，主要驻留在卵泡膜、黄体、闭锁卵泡和间质组织等构成的微环境中；其数目、分布、功能稳态异常可影响卵泡发育（包括卵母细胞成熟和排卵等），与女性不孕相关。卵巢TRM功能障碍会导致卵巢常见疾病发生，如卵巢子宫内膜异位囊肿、多囊卵巢综合征和早发性卵巢功能不全等。综述卵巢TRM的来源、生理功能及其功能异常对卵泡发育的影响机制，并对卵巢TRM功能障碍相关卵巢疾病进行深入探讨，旨在为卵巢功能障碍性疾病的治疗提供新的思路。

关键词: 卵巢, 巨噬细胞, 细胞微环境, 囊肿, 多囊卵巢综合征

Abstract:

In the ovary, there is a complex neuroendocrine and immune regulatory network. Tissueresident macrophages (TRMs) are a kind of innate immune cells that exist in most tissues and organs of human body. TRMs are independent of the peripheral circulation, with the ability of self-renewal. TRMs as the most abundant immune cells in the ovary mainly reside in the microenvironment that is composed of follicular membrane, corpus luteum, atresia follicles and interstitial tissue. The disorder of quantity, distribution and functional homeostasis of ovarian TRMs is related to female infertility, by affecting follicular development (including oocyte maturation and ovulation). The dysfunction of ovarian TRMs could result in the occurrence of common ovarian diseases, including endometriosis, polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI). In this review, we discuss the source and physiological function of ovarian TRMs, the mechanism of ovarian TRMs-related follicular development, and common ovarian diseases-related to the dysfunction of ovarian TRMs, so as to provide a potential treatment way for those ovarian diseases.

Key words: Ovary, Macrophages, Cellular microenvironment, Cysts, Polycystic ovary syndrome

郭艳, 刁瑞英, 苏丹娜, 汪丽萍. 组织驻留巨噬细胞与卵巢常见疾病[J]. 国际生殖健康/计划生育杂志, 2023, 42(4): 323-328.

GUO Yan, DIAO Rui-ying, SU Dan-na, WANG Li-ping. Tissue-Resident Macrophages and Common Ovarian Diseases[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(4): 323-328.

图/表 1

参考文献 33

[1]	Wu R, Van der Hoek KH, Ryan NK, et al. Macrophage contributions to ovarian function[J]. Hum Reprod Update, 2004, 10(2):119-133. doi: 10.1093/humupd/dmh011. doi: 10.1093/humupd/dmh011 pmid: 15073142
[2]	Zhang Z, Schlamp F, Huang L, et al. Inflammaging is associated with shifted macrophage ontogeny and polarization in the aging mouse ovary[J]. Reproduction, 2020, 159(3):325-337. doi: 10.1530/REP-19-0330. doi: 10.1530/REP-19-0330 pmid: 31940276
[3]	Turner EC, Hughes J, Wilson H, et al. Conditional ablation of macrophages disrupts ovarian vasculature[J]. Reproduction, 2011, 141(6):821-831. doi: 10.1530/REP-10-0327. doi: 10.1530/REP-10-0327 pmid: 21393340
[4]	Jokela H, Lokka E, Kiviranta M, et al. Fetal-derived macrophages persist and sequentially maturate in ovaries after birth in mice[J]. Eur J Immunol, 2020, 50(10):1500-1514. doi: 10.1002/eji.202048531. doi: 10.1002/eji.202048531 URL
[5]	Li N, Li Z, Fang F, et al. Two distinct resident macrophage populations coexist in the ovary[J]. Front Immunol, 2022, 13:1007711. doi: 10.3389/fimmu.2022.1007711. doi: 10.3389/fimmu.2022.1007711 URL
[6]	李念娱, 焦雪, 秦莹莹. 性腺组织驻留巨噬细胞的研究进展[J]. 中华生殖与避孕杂志, 2022, 42(4):419-424. doi: 10.3760/cma.j.cn101441-20200901-00472. doi: 10.3760/cma.j.cn101441-20200901-00472
[7]	Sun JX, Xu XH, Jin L. Effects of Metabolism on Macrophage Polarization Under Different Disease Backgrounds[J]. Front Immunol, 2022, 13:880286. doi: 10.3389/fimmu.2022.880286. doi: 10.3389/fimmu.2022.880286 URL
[8]	Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease[J]. J Cell Physiol, 2018, 233(9):6425-6440. doi: 10.1002/jcp.26429. doi: 10.1002/jcp.26429 pmid: 29319160
[9]	Duffy DM, Ko C, Jo M, et al. Ovulation: Parallels With Inflammatory Processes[J]. Endocr Rev, 2019, 40(2):369-416. doi: 10.1210/er.2018-00075. doi: 10.1210/er.2018-00075 pmid: 30496379
[10]	Caillaud M, Duchamp G, Gérard N. In vivo effect of interleukin-1beta and interleukin-1RA on oocyte cytoplasmic maturation, ovulation, and early embryonic development in the mare[J]. Reprod Biol Endocrinol, 2005, 3:26. doi: 10.1186/1477-7827-3-26. doi: 10.1186/1477-7827-3-26
[11]	Zhu Y. Metalloproteases in gonad formation and ovulation[J]. Gen Comp Endocrinol, 2021, 314:113924. doi: 10.1016/j.ygcen.2021.113924. doi: 10.1016/j.ygcen.2021.113924 URL
[12]	赵久华, 郑舒婷, 林凤屏, 等. 免疫细胞在黄体发育及退化过程中的作用[J]. 中国医学科学院学报, 2022, 44(3):504-509. doi: 10.3881/j.issn.1000-503X.13309. doi: 10.3881/j.issn.1000-503X.13309
[13]	Wu J, Carlock C, Zhou C, et al. IL-33 is required for disposal of unnecessary cells during ovarian atresia through regulation of autophagy and macrophage migration[J]. J Immunol, 2015, 194(5):2140-2147. doi: 10.4049/jimmunol.1402503. doi: 10.4049/jimmunol.1402503 pmid: 25617473
[14]	Cui LL, Yang G, Pan J, et al. Tumor necrosis factor α knockout increases fertility of mice[J]. Theriogenology, 2011, 75(5):867-876. doi: 10.1016/j.theriogenology.2010.10.029. doi: 10.1016/j.theriogenology.2010.10.029 URL
[15]	Pepe G, Locati M, Della Torre S, et al. The estrogen-macrophage interplay in the homeostasis of the female reproductive tract[J]. Hum Reprod Update, 2018, 24(6):652-672. doi: 10.1093/humupd/dmy026. doi: 10.1093/humupd/dmy026 pmid: 30256960
[16]	Liang Y, Xie H, Wu J, et al. Villainous role of estrogen in macrophage-nerve interaction in endometriosis[J]. Reprod Biol Endocrinol, 2018, 16(1):122. doi: 10.1186/s12958-018-0441-z. doi: 10.1186/s12958-018-0441-z
[17]	Ono Y, Nagai M, Yoshino O, et al. CD11c+ M1-like macrophages (MΦs) but not CD206+ M2-like MΦ are involved in folliculogenesis in mice ovary[J]. Sci Rep, 2018, 8(1):8171. doi: 10.1038/s41598-018-25837-3. doi: 10.1038/s41598-018-25837-3 pmid: 29802255
[18]	McFee RM, Rozell TG, Cupp AS. The balance of proangiogenic and antiangiogenic VEGFA isoforms regulate follicle development[J]. Cell Tissue Res, 2012, 349(3):635-647. doi: 10.1007/s00441-012-1330-y. doi: 10.1007/s00441-012-1330-y pmid: 22322423
[19]	Rizov M, Andreeva P, Dimova I. Molecular regulation and role of angiogenesis in reproduction[J]. Taiwan J Obstet Gynecol, 2017, 56(2):127-132. doi: 10.1016/j.tjog.2016.06.019. doi: S1028-4559(17)30001-3 pmid: 28420494
[20]	Zeng XY, Xie H, Yuan J, et al. M2-like tumor-associated macrophages-secreted EGF promotes epithelial ovarian cancer metastasis via activating EGFR-ERK signaling and suppressing lncRNA LIMT expression[J]. Cancer Biol Ther, 2019, 20(7):956-966. doi: 10.1080/15384047.2018.1564567. doi: 10.1080/15384047.2018.1564567 URL
[21]	Tan Z, Gong X, Li Y, et al. Impacts of endometrioma on ovarian aging from basic science to clinical management[J]. Front Endocrinol(Lausanne), 2022, 13:1073261. doi: 10.3389/fendo.2022.1073261. doi: 10.3389/fendo.2022.1073261
[22]	Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations[J]. Lancet, 2021, 397(10276):839-852. doi: 10.1016/S0140-6736(21)00389-5. doi: 10.1016/S0140-6736(21)00389-5 pmid: 33640070
[23]	Laganà AS, Salmeri FM, Ban Frangež H, et al. Evaluation of M1 and M2 macrophages in ovarian endometriomas from women affected by endometriosis at different stages of the disease[J]. Gynecol Endocrinol, 2020, 36(5):441-444. doi: 10.1080/09513590.2019.1683821. doi: 10.1080/09513590.2019.1683821 pmid: 31663401
[24]	Liu X, Zhang Q, Guo SW. Histological and Immunohistochemical Characterization of the Similarity and Difference Between Ovarian Endometriomas and Deep Infiltrating Endometriosis[J]. Reprod Sci, 2018, 25(3):329-340. doi: 10.1177/1933719117718275. doi: 10.1177/1933719117718275 pmid: 28718381
[25]	Filippi I, Carrarelli P, Luisi S, et al. Different Expression of Hypoxic and Angiogenic Factors in Human Endometriotic Lesions[J]. Reprod Sci, 2016, 23(4):492-497. doi: 10.1177/1933719115607978. doi: 10.1177/1933719115607978 pmid: 26408396
[26]	Zhang D, Yu Y, Duan T, et al. The role of macrophages in reproductive-related diseases[J]. Heliyon, 2022, 8(11):e11686. doi: 10.1016/j.heliyon.2022.e11686. doi: 10.1016/j.heliyon.2022.e11686 URL
[27]	Xiong YL, Liang XY, Yang X, et al. Low-grade chronic inflammation in the peripheral blood and ovaries of women with polycystic ovarian syndrome[J]. Eur J Obstet Gynecol Reprod Biol, 2011, 159(1):148-150. doi: 10.1016/j.ejogrb.2011.07.012. doi: 10.1016/j.ejogrb.2011.07.012 URL
[28]	Goteri G, Lucarini G, Zizzi A, et al. Proangiogenetic molecules, hypoxia-inducible factor-1alpha and nitric oxide synthase isoforms in ovarian endometriotic cysts[J]. Virchows Arch, 2010, 456(6):703-710. doi: 10.1007/s00428-010-0929-1. doi: 10.1007/s00428-010-0929-1 URL
[29]	Chon SJ, Umair Z, Yoon MS. Premature Ovarian Insufficiency: Past, Present, and Future[J]. Front Cell Dev Biol, 2021, 9:672890. doi: 10.3389/fcell.2021.672890. doi: 10.3389/fcell.2021.672890 URL
[30]	Ishizuka B. Current Understanding of the Etiology, Symptomatology, and Treatment Options in Premature Ovarian Insufficiency (POI)[J]. Front Endocrinol(Lausanne), 2021, 12:626924. doi: 10.3389/fendo.2021.626924. doi: 10.3389/fendo.2021.626924
[31]	Liu P, Zhang X, Hu J, et al. Dysregulated cytokine profile associated with biochemical premature ovarian insufficiency[J]. Am J Reprod Immunol, 2020, 84(4):e13292. doi: 10.1111/aji.13292. doi: 10.1111/aji.13292
[32]	Taghavi SA, Ashrafi M, Mehdizadeh M, et al. Toll-like receptors expression in follicular cells of patients with poor ovarian response[J]. Int J Fertil Steril, 2014, 8(2):183-192. pmid: 25083184
[33]	Briley SM, Jasti S, McCracken JM, et al. Reproductive age-associated fibrosis in the stroma of the mammalian ovary[J]. Reproduction, 2016, 152(3):245-260. doi: 10.1530/REP-16-0129. doi: 10.1530/REP-16-0129 pmid: 27491879